Formaldehyde → Methyl 2-(4-ethyl-3,5-dimethoxy-phenyl)-acrylate

Participants

Reaction Steps

c 1) A solution of 80.43 g (337.5 mmol) of methyl (4-ethyl-3,5-dimethoxy-phenyl)-acetate in 400 ml of toluene was added dropwise to a suspension of 22.1 g (506 mmol) of NaH (55% in mineral oil) in 400 ml of tetrahydrofuran and 40.86 g (346 mmol) of dimethyl oxalate and the mixture was stirred at room temperature for 65 hours. The reaction mixture was poured on to 300 ml of ice-water and washed twice with 250 ml of diethyl ether. The aqueous phase was adjusted to pH 1 with 25% HCl and extracted three times with 300 ml of diethyl ether. The combined phases were dried (MgSO4), filtered and evaporated. The thus-obtained dimethyl 2-(4-ethyl-3,5-dimethoxy-phenyl)-3-oxo-succinate (101.9 g, 314.3 mmol) was suspended in 150 ml of water and treated with 61 ml (812 mmol) of formaldehyde solution (37% in water). Subsequently, a solution of 43.4 g of potassium carbonate in 150 ml of water was slowly added dropwise thereto and the mixture was stirred at room temperature for 12 hours and then extracted three times with 250 ml of diethyl ether. The combined organic phases were dried (MgSO4), filtered and evaporated. Chromatography of the resulting residue (silica gel, hexane/methylene chloride 1:2) gave 44.5 g (53%) of methyl 2-(4-ethyl-3,5-dimethoxy-phenyl)-acrylate as a colorless wax, Rf=0.635 (silica gel, methylene chloride/hexane 2:1).

Provenance & Evidence